The present invention relates to a series of novel complexes of quadricoordinate, divalent platinum with certain specified amino compounds. Such complexes have valuable anti-tumor activity with better solubility than known anti-tumor platinum compounds and complexes. The invention also provides a process for preparing these complexes and methods and compositions using them.
Cancerous disorders are a major medical problem but are often difficult to cure. The main reason for this is that the differences between tumor cells and normal cells are generally extremely small, with the result that compounds which are toxic to tumor cells are also toxic to normal cells. The chemotherapy of cancerous disorders is therefore generally dependent upon very limited differences between the susceptibilities of tumor cells and of normal cells to anti-tumor agents.
Various platinum compounds are known to have anti-tumor activities. For example cisplatin [Rosenberg et al, Nature 222, 385 (1965) and The Merck Index, tenth edition (1983) monograph 2289] has been successfully used in the treatment of tumors, and malonato-(1,2-diaminocyclohexane)platinum(II) [e.g. U.S. Pat. No. 4,169,846 and Kidani et al, Gann, 71, 637-643 (1980)] has also been proposed for such use. Both of the above platinum complexes have some structural similarity to the compounds of the invention. Another platinum complex, although structurally less similar to the compounds of the invention, which has recently become available for the treatment of tumors is carboplatin [Drugs of the Future, Vol. 8, No. 6, 489-491 (1983)]. However, most of the known platinum complexes, including those referred to above, have a high renal toxicity and a poor solubility in water, which makes it difficult to formulate them into an appropriate dosage form.
Another series of platinum complexes with a limited structural resemblance to the compounds of the present invention are disclosed in U.S. patent application Ser. No. 902,420, filed 29 Aug. 1986.
We have now discovered a novel series of platinum complexes which have good anti-tumor activity but relatively few side effects, such as renal toxicity and bone marrow suppression, and which have a good solubility in water.